Developing and testing new vaccines is an essential component of efforts supported by the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID). Since many pathogens either colonize mucosal surfaces or invade through them, the Division has long supported research to define protective mucosal immune responses. Because mucosal immune responses play essential roles in containing and eliminating several pathogens and because orally administered vaccines offer clear advantages over injected preparations, the Division wishes to establish a focused research component to develop methods to deliver immunogens to mucosal tissues (primarily intestinal) and to enhance the resultant immune responses. The Mucosal Immunization Research Group (MIRG) will study two major issues: antigen delivery and immune enhancement. This work will include research and development efforts on (1) methods such as microencapsulation, which provide the dual functions of protecting the immunogen from degradation and releasing it into the body at sites and times that are optimal for immune responses; and (2) vaccine vectors such as Salmonella, adenovirus, or other organisms, which express the target immunogen once they begin replicating within the host. (This contract will not fund studies to design and construct vaccine vectors, but it will be used to test vectors developed with other support.) This contract will also support basic immunological research on the regulation of mucosal immune responses and methods to modify these responses (e.g., adjuvants).